South Sydney forward Sam Burgess is among the latest withdrawals from England's training squad.
The former Bradford favourite, who has been a huge success in Australia's National Rugby League, is to undergo knee surgery.
Warrington duo Ryan Atkins (shoulder) and Ben Westwood (knee and groin) are to have surgery following their club's defeat by Leeds in Saturday's Super League Grand Final at Old Trafford.
England coach Steve McNamara was also denied the services of Gareth Widdop (Melbourne), Jack Reid (Brisbane), Eorl Crabtree (Huddersfield), Jon Wilkin (St Helens) and Danny Tickle (Hull) through injury when he named his 24-man squad last week.
Former St Helens captain James Graham, now with Canterbury Bulldogs, was withdrawn after he was handed a 12-match ban for biting and has been replaced by Luke Burgess, the older brother of Sam.
With Gareth Ellis having left Wests Tigers to take up a three-year contract with Hull, Luke Burgess will be the only Australia-based player in McNamara's squad for a 10-day high-altitude camp in South Africa and the autumn internationals.
The latest call-ups are Wigan second rower Liam Farrell and Warrington pair Ben Harrison and Stefan Ratchford.
Farrell and Ratchford were in the England team that played the Exiles this summer while Harrison went on the 2010 Four Nations tour to Australia and New Zealand.
The squad leave Manchester Airport for Potchefstroom on Wednesday and will return in time for England's opening match in the autumn international series against Wales in Wrexham on Saturday, October 27 (2.30pm).